Myelodysplastic Syndrome (MDS) with inv(3)(q21q26) or t(3;3)(q21q26): A Spectrum of Diseases with a High Risk for Progression to Acute Myeloid Leukemia (AML)
W Cui, J Sun, LJ Medeiros, P Lin. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: inv(3)(q21q26) or t(3;3)(q21q26) are rare recurrent aberrations observed in MDS, AML or myeloproliferative neoplasm (MPN) in blast phase. The natural history of MDS with inv(3) or t(3;3) is less known.
Design: De novo or therapy related MDS (t-MDS) cases with inv(3) or t(3;3) detected by conventional cytogenetics were identified and compared.
Results: We identified 17 cases, of which 11 were classified as de novo and 6 as t-MDS. The median age was 64 years (range, 15-77 years). The de novo MDS cases were originally classified as: refractory anemia (RA) (n=1), refractory anemia with ring sideroblasts (RARS) (n=3), refractory cytopenia with multilineage dysplasia (RCMD) (n=2), refractory anemia with excess of blasts (RAEB) (n=3), and chronic myelomonocytic leukemia-2 (CMML-2) (n=1). The t-MDS cases were classified as: RCMD (n=2) and RAEB (n=4). Using the International Prognostic Scoring System (IPSS), 7 de novo and 4 t-MDS cases had an initial score in the range of low to intermediate-2. The inv(3) or t(3;3) was the sole abnormality in 6 (36%) cases. The remaining cases had additional aberrations, with -7/7q or -5/5q being most common, in 8 and 6 cases, respectively. Three cases had +8 and 5 cases had a complex karyotype with additional 6 or more abnormalities. Progression to AML occurred in 11 (65%) patients after an interval of 2.5-158 months (median: 9.5 months), and 10 patients died of AML. At the last follow up, 15 patients died with a median survival (MS) of 19.5 and 9 months for de novo and t-MDS cases, respectively.
Conclusions: MDS cases with inv(3) or t(3;3) are clinically and pathologically heterogeneous. However, nearly 2/3 of cases progressed to AML. Cases of de novo and t-MDS were similar in their demographic features, cytogenetic aberrations, risk for progression to AML and survival. Initial IPSS scores were not predictive of outcome. There was no correlation between the presence or type of cytogenetic aberrations in addition to inv(3) or t(3;3) with survival.
|Age (median, range: yrs)||inv(3)/t(3;3) only||-7/7q||-5/5q||Complex||p-AML||MS, (-7/7q), mos|
|De novo MDS (n=11)||65 (23-75)||4 (36%)||4 (36%)||4 (36%)||2 (18%)||7 (64%)||12.8|
|t-MDS (n=6)||53 (15-77)||2 (33%)||4 (67%)||2 (33%)||3 (50%)||4 (67%)||9.8|